Stable and temperature-sensitive transformation of rat kidney epithelial cells suppresses expression of acidic fibroblast growth factor 1 but activates secretion of fibroblast growth factor 3 (int-2) and vascular endothelial growth factor

Cell Growth Differ. 1994 Apr;5(4):349-57.

Abstract

Rat kidney proximal tubule epithelial cells (RPTE) in primary culture express acidic fibroblast growth factor 1 (FGF-1). Transformation of RPTE by SV40 (SV-RPTE) suppressed FGF-1 expression but activated secretion of FGF-like factor(s). SV-RPTE conditioned medium contained growth-promoting activity for SV-RPTE and human umbilical vein endothelial cells, indicating that both autocrine and angiogenic factors were secreted. Reverse transcriptase-polymerase chain reaction and Northern analysis for various FGFs showed that only FGF-3, also known as int-2, mRNA was expressed in SV-RPTE. In addition, expression of mRNA for the heparin-binding angiogenic factor vascular endothelial growth factor (VEGF) increased dramatically in SV-RPTE. Physical characterization of the activity in the SV-RPTE conditioned medium suggested that FGF-3 and VEGF contributed the autocrine and angiogenic activities, respectively. We also investigated FGF-3 and VEGF secretion in temperature-sensitive (ts) SV40-transformed RPTE. tsSV-RPTE had transformed properties resembling those of SV-RPTE only at the permissive temperature (33 degrees C), e.g., increased growth potential and anchorage-independent growth. FGF-1 was expressed only at the nonpermissive temperature. VEGF mRNA levels and secretion of the human umbilical vein endothelial cell growth-promoting activity were reduced by switching tsSV-RPTE cells from 33 degrees to 39 degrees C. However, FGF-3 mRNA levels were not affected significantly by the temperature switch suggesting that activation of VEGF and FGF-3 occurs through different mechanisms. These results indicate that FGF-1 expression in RPTE is suppressed by SV40 transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Animals
  • Cell Line
  • Cell Transformation, Viral / physiology*
  • Endothelial Growth Factors / metabolism*
  • Epithelial Cells
  • Epithelium / physiology
  • Fibroblast Growth Factor 1 / metabolism*
  • Fibroblast Growth Factor 3
  • Fibroblast Growth Factors / metabolism*
  • Growth Substances / metabolism
  • Hot Temperature
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / physiopathology*
  • Lymphokines / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Simian virus 40 / physiology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Fgf3 protein, rat
  • Fibroblast Growth Factor 3
  • Growth Substances
  • Lymphokines
  • Proto-Oncogene Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 1
  • Fibroblast Growth Factors